Transforming the understanding of brain immunity

Science, Journal Year: 2023, Volume and Issue: 380(6640)

Published: April 6, 2023

Contemporary studies have completely changed the view of brain immunity from envisioning as isolated and inaccessible to peripheral immune cells an organ in close physical functional communication with system for its maintenance, function, repair. Circulating reside special niches brain's borders, choroid plexus, meninges, perivascular spaces, which they patrol sense a remote manner. These niches, together meningeal lymphatic skull microchannels, provide multiple routes interaction between system, addition blood vasculature. In this Review, we describe current ideas about their implications aging, diseases, immune-based therapeutic approaches.

Language: Английский

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Brain borders at the central stage of neuroimmunology

Nature, Journal Year: 2022, Volume and Issue: 612(7940), P. 417 - 429

Published: Dec. 14, 2022

Language: Английский

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Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1309 - 1327

Published: March 1, 2023

Language: Английский

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Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment

Cell, Journal Year: 2022, Volume and Issue: 185(26), P. 5028 - 5039.e13

Published: Dec. 1, 2022

Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on from 45 cognitively normal subjects ranging 54 to 82 years old. We uncovered an upregulation of lipid transport genes in monocytes age. then compared this cohort 14 impaired subjects. In subjects, downregulation occurred concomitantly cytokine signaling CD8 T cells. Clonal effector memory cells upregulated C-X-C motif chemokine receptor 6 (CXCR6) The CXCR6 ligand, ligand 16 (CXCL16), was elevated the suggesting CXCL16-CXCR6 as mechanism for antigen-specific cell entry into brain. Cumulatively, these results reveal cerebrospinal dysregulation during healthy brain and cognitive impairment.

Language: Английский

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Conserved meningeal lymphatic drainage circuits in mice and humans

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(8)

Published: July 1, 2022

Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of dura mater, where they ensure waste product elimination immune surveillance brain tissues. Whether MLVs exist anterior part murine human skull how connect with glymphatic system extracranial lymphatics remained unclear. Here, we used light-sheet fluorescence microscopy (LSFM) imaging mouse whole-head preparations after OVA-A555 tracer injection into cerebrospinal fluid (CSF) performed real-time vessel-wall (VW) magnetic resonance (VW-MRI) systemic gadobutrol patients neurological pathologies. We observed a conserved three-dimensional anatomy mice humans that aligned dural venous sinuses but not nasal CSF outflow, discovered an extended MLV network around cavernous sinus, exit routes through foramina emissary veins. VW-MRI may provide diagnostic tool for drainage defects diseases.

Language: Английский

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Bone marrow hematopoiesis drives multiple sclerosis progression

Cell, Journal Year: 2022, Volume and Issue: 185(13), P. 2234 - 2247.e17

Published: June 1, 2022

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive in MS unknown. Here, we report that bone HSPCs are skewed toward myeloid lineage concomitant clonal expansion patients. Lineage tracing experimental encephalomyelitis, mouse model MS, reveals remarkable myelopoiesis an augmented output neutrophils Ly6Chigh monocytes invade CNS. We found myelin-reactive preferentially migrate into compartment CXCR4-dependent manner. This aberrant involves CCL5-CCR5 axis augments CNS inflammation demyelination. Our study suggests targeting niche presents avenue to treat other disorders.

Language: Английский

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Identification of direct connections between the dura and the brain

Nature, Journal Year: 2024, Volume and Issue: 627(8002), P. 165 - 173

Published: Feb. 7, 2024

Language: Английский

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Distinct molecular profiles of skull bone marrow in health and neurological disorders

Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3706 - 3725.e29

Published: Aug. 1, 2023

The bone marrow in the skull is important for shaping immune responses brain and meninges, but its molecular makeup among bones relevance human diseases remain unclear. Here, we show that mouse has most distinct transcriptomic profile compared with other states of health injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals distinct, differentially expressed neutrophil-related pathways unique synaptic protein signature. 3D imaging demonstrates structural cellular details skull-meninges connections (SMCs) veins. Last, using translocator positron emission tomography (TSPO-PET) imaging, reflects inflammatory disease-specific spatial distribution patients various neurological disorders. anatomical functional potential as site diagnosing, monitoring, treating diseases.

Language: Английский

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Functional analysis of the human perivascular subarachnoid space

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 5, 2024

Abstract The human subarachnoid space harbors the cerebrospinal fluid, which flows within a landscape of blood vessels and trabeculae. Functional implications anatomy remain far less understood. This study 75 patients utilizes fluid tracer (gadobutrol) consecutive magnetic resonance imaging to investigate features early (i.e. 2-3 h after injection) propagation space. There is time-dependent perivascular pattern enrichment antegrade along major cerebral artery trunks; anterior-, middle-, posterior arteries. correlation between time first around arteries in nearby cortex significant. These observations suggest existence compartmentalized space, where ensheathment facilitates passage towards brain tissue. Periarterial transport impaired subjects with reduced intracranial pressure-volume reserve capacity idiopathic normal pressure hydrocephalus who also show increased size.

Language: Английский

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Cellular senescence, DNA damage, and neuroinflammation in the aging brain

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(6), P. 461 - 474

Published: May 9, 2024

Language: Английский

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